OBJECTIVES: To understand how androgens exert their stimulatory effect on normal and neoplastic prostate. Special emphasis is given to the role of 5alpha-reduction of testosterone and binding of Dihydrotestosterone (DHT) to receptors in sensitive cells. APPROACH: If formation of DHT from testosterone by the action of 5 alpha-reductase in target cells is a necessary step in the mechanism of androgenic stimulation, the inhibition of this reaction by suitable means should deprive the cells of the androgenic stimulus. We have studied the structural characteristics of steroid competitive inhibitors of the 5alpha-reduction of testosterone and the most effective ones have been shown to possess antiandrogenic properties in bio-assays. We plan to study the effects of these inhibitors in an animal model of prostatic carcinoma such as R-3327 tumors of Copenhagen rats. We also propose to study the role of cytoplasmic receptors for DHT in the tissue response to androgens. It is speculated that androgen sensitive prostatic tumors should have receptors for DHT while androgen insensitive ones should not.